Is AP3B1 p.Pro511Ser (c.1531C>T) pathogenic?

AP3B1 p.Pro511Ser (c.1531C>T) is classified Uncertain significance in AP3B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-29). AlphaMissense: ambiguous (0.3757); Absent from gnomAD v4.1; Associated with Hermansky-Pudlak syndrome 2.

What condition is associated with AP3B1 p.Pro511Ser (c.1531C>T)?

AP3B1 p.Pro511Ser (c.1531C>T) is associated with Hermansky-Pudlak syndrome 2 (ClinVar).

How common is AP3B1 p.Pro511Ser (c.1531C>T) in the general population?

AP3B1 p.Pro511Ser (c.1531C>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AP3B1 p.Pro511Ser (c.1531C>T)?

AlphaMissense predicts ambiguous (score 0.3757) — an in-silico prediction, not a clinical call.

AP3B1 p.Pro511Ser

c.1531C>T · rs2531030298 · VCV2824799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hermansky-Pudlak syndrome 2

Computational evidence

Protein change
AlphaMissense	0.3757	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -11.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 213 kb · p 0.0039 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AP3B1
Protein: p.Pro511Ser
Coding: c.1531C>T
MANE Select: NM_003664
dbSNP: rs2531030298
Type: single nucleotide variant
Location: chr5:78141262 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.85 · 5 PDB

Full AP3B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

AP3B1 c.2078-1G>A Likely pathogenic ★★ same condition
AP3B1 c.280-2A>G Likely pathogenic ★★ same condition
AP3B1 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B1 p.Arg649Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B1 c.128+4A>G Uncertain significance ★★ same condition
AP3B1 c.2077+6T>C Uncertain significance ★★ same condition
AP3B1 c.2809+4A>G Uncertain significance ★★ same condition
AP3B1 c.2992+3G>A Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ap3b1-p-pro511ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown